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Synthesis of constrained l-phenylalanine derivatives incorporating a benzazepinone or an azepinone ring as VCAM/VLA-4 antagonists

✍ Scribed by Achyutharao Sidduri; Jian Ping Lou; Robert Campbell; Karen Rowan; Jefferson W Tilley


Publisher
Elsevier Science
Year
2001
Tongue
French
Weight
96 KB
Volume
42
Category
Article
ISSN
0040-4039

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✦ Synopsis


Novel constrained L-phenylalanine derivatives incorporating a benzazepinone or an azepinone ring were synthesized in 13 and 8 steps, respectively, employing a key base-catalyzed intramolecular cyclization reaction. The product, 2, was comparable in potency in a VCAM/VLA-4 ELISA assay to the corresponding unconstrained analog 1 suggesting that cyclization favored the bioactive conformation. However, compound 4 was 100-fold less potent than the unconstrained analog 3.